The Protheans are an extinct race that mysteriously vanished from the Galaxy 50,000 years ago. They were the only species of their time to achieve space flight and their empire dominated Citadel space. The Protheans are credited with creating the Citadel and the Mass Relays which are still considered the greatest technological achievements in the galaxy.
The entire species disappeared around 50,000 years ago, but many of their ancient ruins still stand on planets like Feros, Therum and Ilos. It appears the Protheans also scouted and studied other species long before they achieved space flight. The Hanar worship the Protheans like gods. They refer to them as the 'Enkindlers' and believe they a responsible for giving the Hanar sentience and language.
The Humans also have to credit the Protheans for helping them achieve faster-than-light space travel. In 2148 the humans discovered a Prothean data cache deep under the surface of Mars, meaning that the Protheans were likely studying humans 50,000 years ago. The data cache had traces of a mysterious substance called Element Zero. This allowed humans to travel further into the Sol System and eventually discover a Mass Relay near Pluto. The Protheans made observation on primitive species.
Despite popular belief, the Protheans didn't create the Mass Relays or the Citadel, they just stumbled across them while exploring the Galaxy, much like many races before them. The Citadel would become the center of galactic civilization for every species that discovered it. The Citadel and the Mass Relays would allow the technology of every species that discovered them to massively advance. Then, once the species of the Galaxy were reaching their peak in technology, the Reapers would appear through a secret Mass Relay behind the Citadel and destroy all traces of the Citadel species.
The Protheans were on the verge of creating their own Mass Relay called the Conduit when they were struck down by the Reapers. First they attacked the Citadel, destroyed the Prothean Government and cut all communications between the Citadel and the Prothean systems. They also gain access to the main data catalogue on the Citadel which had information on every Prothean System and all the Protheans living on each system. In the centuries that followed, the Reapers would travel the Galaxy destroying every Prothean in existence except Javik who went into a stasis pod. The Protheans were indoctrinated and turned into Collectors.
Luckily, during the original attack on the Citadel, data about the Science team working on the Conduit in Ilos was destroyed so the planet avoided the wrath of the Reapers. The scientists working there agreed to go into stasis pods until the Reaper threat was over. They left a Virtual Intelligence called Vergil in charge of the stasis pods. However, the Protheans underestimated how long it would take the Reapers to complete their genocide of the Prothean race. As the centuries passed, thousands of the stasis pods were shut down to help conserve energy. In the end, only a dozen of the top scientists were left. They knew the chance of saving their race was dire and instead dedicated their lives to finding out where the Reapers came from and how to stop future species from suffering the same fate. They sent out distress calls through Prothean Beacons to warn any remaining Protheans or any future races about what happened. They also discovered that the Keepers were vital to the Reapers gaining entrance into the Citadel. The scientists used the Conduit to travel to the Citadel after the Reaper threat had gone and interfered with a signal that alerts the keepers to activate the Citadel relay. They believed they has trapped the Reapers in dark space but had no way of knowing until the next time the attacks. The fate of the Prothean scientists is unknown, but it's likely that they died on the Citadel. The Conduit between Ilos and the Citadel was one way only so they were stuck on the Citadel. Because the Citadel was completely wiped out, it's likely that they ran out of food and died.